Reissert’s compound

Another 10 g. (11%) of impure 2-benzoyl-l-cyano-l-methyl-1,2-dihydroisoquinoline may be obtained by adding water to the cold mother liquor until it becomes turbid. The mixture is heated until the turbidity disappears, and the resulting solution is cooled slowly, then refrigerated. The additional product obtained by this method is contaminated with Reissert s compound and should not be used in the next step if pure 1-methyl-isoquinoline is desired. 

Reductive oxidation of />-nitrotoluene to -aminobenzaldehyde, 31, 6 Reformatsky reaction, 37, 38 Reissert s compound, 38, 58 Reissert reaction, 38, 58 Replacement, benzenesulfonate groups by bromine atoms, 31, 82 bromine, by a thiol group, 30, 35 by fluorine, 36, 40 chlorine, by an amino group, 31,45 by a thiol group, 32, 101 by iodine, 30, 11 by methoxyl, 32, 79 by nitrile, 36, 50 in an imido-chloride group by an anilino group, 31, 48 chlorine and nitro by ethoxyl radicals, 32,68... 

Carbanion formation. Makosza1 has used the combination of benzyltriethylammonium chloride and sodium hydroxide as the base for alkylation of phenyl-acetonitrile with alkyl halides and with halonitrobenzenes. The same combination was found to be superior to phenyllithium (used previously2) for alkylation of Reissert s compound (N-benzoyl-1,2-dihydroisoquinaldonitrile).3... 

A. l-Cyano-2-benzoyl-l,2-dihydroisoquinoline Reissert s compound ) (Note 1). In a 5-1. thrce-necked flask equipped with a Hershberg stirrer, a dropping funnel, and a condenser is jilaced a. 

Reissert s compound (l-cyano-l,2-dihydroquinolinyl benzamide) is apparently de-protonated under phase transfer conditions at the one-carbon as expected. The condensation of the carbanion with an aldehyde or ketone leads to an N-benzoyl alk-oxide in which oxygen acylation (N ->0 acyl transfer) results in five-membered ring formation. The intermediate oxazolidine decomposes with loss of cyanide to give the benzoate ester of an isoquinolinoylcarbinol as shown in equation 10.26 [36]. 

Qu tern iy S Its. The ring nitrogen of quinoline reacts with a wide variety of alkylating and acylating agents to produce useful intermediates like A/-benzoylquinolinium chloride [4903-36-0] (8). The quinoline 1,2-adducts, eg, A/-benzyl-2-cyano-l,2-dihydroquinoline [13721 -17-0] (9), or Reissert compounds (28), formed with potassium cyanide can produce 2-carboxyquinoline [93-10-7] (10) or 2-cyanoquinoline [11436-43-7] (11). 

Reformatsky reaction, 511, 599 Reissert compounds, 150 Resistomycin, 450 Resorcinols, 66, 460-461 Retinal, 120 Retrolactonization, 17 Rhodium(ll) carboxylates, 458-460 Rhodium catalysts, 460 Rhodium(III) chloride, 460-461 Rhodium(III) porphyrins, 461-462 Rifamyem S, 133, 134 Ruthenium(III) chloride, 462 Ruthenium tetroxide, 462-463... 

FMOC-protected amino acid fluorides afford the expected Reissert adducts 160 with a good stereoselectivities, the a-sulfonylamino acid fluorides undergo cycliza-tion to adduct 161 [47, 140, 141], Itho s protocol is amenable to using silyl enol ethers 157 as nucleophiles [142], Gibson has used bulky asymmetric acid chlorides as substrates in a Reissert reaction with TMS-CN the corresponding Reissert compound was then treated with aldehydes and sodium hydride to obtain the enantiopure adducts 4 (Scheme 3) [143],... 

Most activity in this area has centered around the isolation of so-called pseudo-bases (82) in which the cyano group is replaced by a hydroxy group. Thus the pseudo-base is obtained, in addition to the normal Reissert compound, from S-nitroisoquinoline, " 3-methyl-5-nitroisoquinoline, 6-nitroquinoline, and phthalazine. Heating the pseudo-bases in alcohol gives rise to the ethers 83. A discussion of some of the chemistry and properties of the pseudo-bases has appeared. The formation of the pseudo-bases can be suppressed and that of the Reissert compounds increased by the use of a phase-transfer catalyst. Pseudo-bases have also been obtained in attempts to form Reissert compounds from 1,6-naphthyridine and 4,6-phenanthroline. 2-Phenyl-1,2,3-thiadiazole and benzoyl chloride in the presence of cyanide gave 84 and imidazo[l,5-a]pyrazines with acid chloride gave 85 in reactions analogous to the pseudo-base formation. 

In an alternative synthesis of ( )-64 by MacLean s group 120), the pyridone 145 was treated with MeLi in tetrahydrofuran at -78°C to afford, after reduction with NaBH, a mixture of ( )-142 and ( )-143. Debenzyl-ation of the mixture by catalytic hydrogenolysis furnished ( )-64 and ( )-144 in 20 and 40% yields, respectively. In yet another synthesis of ( )-64, Reimann and Renz 122) obtained the 8-methylisoquino[2,l-6][2,7]naph-thyridinium salt 149 by alkylation of the Reissert compound 146 with the 4-chloromethylpyridine derivative 147 in N,N-dimethylformamide in the presence of NaH and subsequent treatment of the resulting 1-substituted isoquinoline (148) with hydrochloric acid in EtOH. Reduction of 149 with NaBH, in MeOH gave ( )-142 and ( )-143 in 9 and 34% yields, respectively. Separate debenzylations of ( )-142 and ( )-143 with hydrochloric acid in EtOH furnished ( )-64 and ( )-144, respectively, in good yields. 

Reissert compounds 13, 835 Garbitol s. Diethylene glycol monoethyl ether Garbobenzhydryloxyl... 

J. Knabe and A. Frie, Arch. Pharm., 306, 648 (1973). For a versatile new synthesis of Reissert compounds using an acid chloride and trimethylsilyl cyanide in methylene chloride, see S. Ruchirawat, N. Phadungkul, M. Chuankamnerdkarn, and C. Thebtara-nonth, Heterocycles, 6, 43 (1977). 

Popp FD, Veeraraghavan S 1982 Synthesis of potential antineoplastic agents. XXVII. (Reissert compound studies. XLIV.). The ellipticine Reissert compounds as an intermediate in the syntheses of ellipticine analogs. J Heterocycl Chem 19 1275-1280... 

N-macrocyclics nitro compounds, N-heterocyclic oxo-N-heterocyclics polynitro-N-heterocyclics Reissert compounds (s. a. under Heterocyclics, special)... 

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